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BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Combined clinical pretest probability (PTP) and D-dimer testing have great diagnostic value for pulmonary embolism exclusion. To harmonize performance levels of D-dimer assays available on the market, the Clinical and Laboratory Standard Institute (CLSI) has published a guideline, endorsed by the US Food and Drug Administration (FDA). Such guideline specifies the ideal D-dimer assay characteristic and target population. This study was conducted following the CLSI guideline to upgrade the assay-intended use and obtain FDA clearance of STA-Liatest D-Di assay for pulmonary embolism exclusion in patient with low/moderate PTP. This was an international, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard of care setting. D-dimer assay was performed in consecutive, ambulatory outpatients suspected of pulmonary embolism, with low/moderate PTP, and without medical conditions or in clinical settings known to alter default D-dimer values regardless of the presence of thrombosis using a threshold of 0.5 μg/ml (fibrinogen equivalent units) for venous thromboembolism exclusion. Results were used to determine test performance. Of 1141 patients who underwent D-dimer testing, 1060 had valid results and completed study as planned. STA-Liatest D-Di assay performance has exceeded the CLSI/FDA guidance requirements, with a sensitivity of 97.6% (95% confidence interval: 91.7–99.7%) and a negative predictive value of 99.7% (95% confidence interval: 99.0–100%). STA-Liatest D-Di assay has an excellent performance when used in combination with a PTP score in relevant patients and has the potential to minimize the economic healthcare burden avoiding unnecessary and expensive imaging tests.